U.S. patent application number 12/871745 was filed with the patent office on 2012-03-01 for adhesive structure with stiff protrusions on adhesive surface.
Invention is credited to Kevin COOPER, Noha ELMOUELHI, Audrey Yoke Yee HO, Chee Tiong LIM, Hong Yee LOw, Sriram NATARAJAN, Isabel RODRIGUEZ, Murty N. VYAKARNAM.
Application Number | 20120052234 12/871745 |
Document ID | / |
Family ID | 44860497 |
Filed Date | 2012-03-01 |
United States Patent
Application |
20120052234 |
Kind Code |
A1 |
NATARAJAN; Sriram ; et
al. |
March 1, 2012 |
ADHESIVE STRUCTURE WITH STIFF PROTRUSIONS ON ADHESIVE SURFACE
Abstract
An adhesive structure is provided comprising a surface from
which extend substantially cylindrical protrusions comprising a
stiff resin having a Young's modulus of greater than 17 MPa. The
protrusions are of sufficiently low diameter to promote adhesion by
physical attractive forces, e.g., Van der Waals attractive forces,
as measured by shear adhesion between the adhesive structure and a
target surface. A method for preparing the structure is provided as
well as a combination of the adhesive structure and target
surface.
Inventors: |
NATARAJAN; Sriram;
(Bridgewater, NJ) ; COOPER; Kevin; (Flemington,
NJ) ; ELMOUELHI; Noha; (Randolph, NJ) ;
VYAKARNAM; Murty N.; (Bridgewater, NJ) ; LOw; Hong
Yee; (Singapore, SG) ; RODRIGUEZ; Isabel;
(Singapore, SG) ; LIM; Chee Tiong; (Singapore,
SG) ; HO; Audrey Yoke Yee; (Singapore, SG) |
Family ID: |
44860497 |
Appl. No.: |
12/871745 |
Filed: |
August 30, 2010 |
Current U.S.
Class: |
428/99 ; 264/313;
73/105 |
Current CPC
Class: |
A61B 2017/00938
20130101; A61B 2017/00942 20130101; B29C 33/52 20130101; A61L
24/106 20130101; A61B 2017/00871 20130101; A61L 24/046 20130101;
A61L 24/0042 20130101; A61B 2017/00951 20130101; Y10T 428/24008
20150115; A61L 24/06 20130101; C09J 2301/31 20200801; C09J 2423/106
20130101; B29C 33/424 20130101; C09J 2467/006 20130101; A61L 24/06
20130101; C08L 67/04 20130101; A61L 24/046 20130101; C08L 23/12
20130101 |
Class at
Publication: |
428/99 ; 73/105;
264/313 |
International
Class: |
B32B 3/06 20060101
B32B003/06; B28B 7/34 20060101 B28B007/34; G01B 5/28 20060101
G01B005/28 |
Claims
1. An adhesive structure comprising a surface from which extend
protrusions comprising a resin having a Young's modulus of greater
than 17 MPa, which protrusions are of sufficiently low diameter to
promote adhesion by increasing physical attractive forces between
the adhesive structure and a target surface, as measured by shear
adhesion.
2. The adhesive structure of claim 1 wherein the protrusions have
an average diameter ranging from 0.2 to 5 microns, an average
length greater than 2 microns and an aspect ratio (length/diameter)
of 1 to 33.
3. The adhesive structure of claim 2 wherein the protrusions have
an average diameter ranging from 0.2 to 2 microns, an average
length greater than 3 microns and an aspect ratio (length/diameter)
of 2 to 30.
4. The adhesive structure of claim 1 wherein the structure is
integrally molded from a resin selected from at least one of
thermoplastic resin, thermosetting resin, and curable resin.
5. The adhesive structure of claim 1 wherein the resin comprises at
least one polymer having a Young's modulus of greater than 17
MPa.
6. The adhesive structure of claim 5 wherein the resin comprises at
least one polymer having a Young's modulus ranging from 20 MPa to 5
GPa.
7. The adhesive structure of claim 5 wherein the polymer is
selected from at least one of a thermoplastic polymer.
8. The adhesive structure of claim 7 wherein the polymer is
selected from at least one of poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), poly(trimethylene
carbonate), poly(caprolactone-co-glycolide) and polypropylene
(PP).
9. The adhesive structure of claim 1 wherein the resin is
hydrophobic.
10. The adhesive structure of claim 9 wherein the hydrophobic resin
comprises a polymer selected from aliphatic polyesters, and
polypropylene.
11. The adhesive structure of claim 1 wherein the resin is
hydrophilic.
12. The adhesive structure of claim 11 wherein the hydrophilic
resin comprises a polymer selected from polyoxaesters, hyaluronic
acids, and polyvinyl alcohols.
13. The adhesive structure of claim 5 wherein the polymer is a
biodegradable polymer selected from aliphatic polyesters, poly
(amino acids), copoly (ether-esters), polyalkylenes oxalates,
tyrosine-derived polycarbonates, poly (iminocarbonates),
polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters
containing amine groups, poly (anhydrides), polyphosphazenes,
collagen, elastin, hyaluronic acid, laminin, gelatin, keratin,
chondroitin sulfate, polyglycolide (PGA), poly(propylenefumarate),
polycyanoacrylate, polycaprolactone (PCL), poly(glycerol sebacate)
(PGS), poly(glycerol sebacate acrylate) (PGSA), and biodegradable
polyurethanes.
14. The adhesive structure of claim 5 wherein the polymer is a
non-biodegradable polymer selected from acrylics, polyamide-imide
(PAI), polyetherketones (PEEK), polycarbonate, polyethylenes (PE),
polybutylene terephthalates (PBT), polyethylene terephthalates
(PET), polypropylene, polyamide (PA), polyvinylidene fluoride
(PVDF), and polyvinylidene fluoride-co-hexafluoropropylene
(PVDF/HFP), polymethylmethacrylate (PMMA), polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate (PHEMA), poly(N-isopropylacrylamide)
(PNIPAAm) and polyolefins.
15. The adhesive structure of claim 1 wherein the surface is
substantially planar and the protrusions are within .+-.45 degrees
of normal to the planar surface.
16. The adhesive structure of claim 1 having a density of
protrusions on its surface ranging from about 1.times.10.sup.5 to
about 6.times.10.sup.8 protrusionsper cm.sup.2.
17. The adhesive structure of claim 1 wherein at least a portion of
the adhesive structure has a dry adhesive strength of at least 3
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
18. The adhesive structure of claim 1 wherein at least a portion of
the adhesive structure has a wet adhesive strength of at least 0.5
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
19. The adhesive structure of claim 5 wherein the polymer is
selected from at least one of poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), and polypropylene (PP)
and adhesion is measured by adhesive force measurements and ranges
from 0.1 to 0.5 N/cm.sup.2 on a target surface having a roughness
of 0.1 to 8 microns.
20. The adhesive structure of claim 1 which is at least partially
formed by a process selected from nanomolding using a template,
polymer self-assembly, lithography, and etching.
21. An adhesive structure comprising a two-sided substrate from
each side of which extend protrusions comprising one or more resins
having a Young's modulus of greater than 17 MPa, which protrusions
are of sufficiently low diameter to promote adhesion by increasing
physical attractive forces between the adhesive structure and a
target surface, as measured by shear adhesion.
22. The adhesive structure of claim 21 wherein the protrusions have
an average diameter ranging from 0.1 to 5 microns, an average
length greater than 2 microns and an aspect ratio (length/diameter)
of 1 to 50.
23. The adhesive structure of claim 22 wherein the protrusions have
an average diameter ranging from 0.1 to 2 microns, an average
length greater than 3 microns and an aspect ratio (length/diameter)
of 2 to 30.
24. The adhesive structure of claim 21 wherein the structure is
integrally molded from a resin selected from at least one of
thermoplastic resin, thermosetting resin, and curable resin.
25. The adhesive structure of claim 21 wherein a resin comprises at
least one polymer having a Young's modulus of greater than 17
MPa.
26. The adhesive structure of claim 25 wherein a resin comprises at
least one polymer having a Young's modulus ranging from 20 MPa to 5
GPa.
27. The adhesive structure of claim 25 wherein the polymer is
selected from at least one of a thermoplastic polymer.
28. The adhesive structure of claim 27 wherein the polymer is
selected from at least one of poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), and polypropylene
(PP).
29. The adhesive structure of claim 21 wherein a resin is
hydrophobic.
30. The adhesive structure of claim 29 wherein the hydrophobic
resin comprises a polymer selected from aliphatic polyesters, and
polypropylenes.
31. The adhesive structure of claim 21 wherein a resin is
hydrophilic.
32. The adhesive structure of claim 31 wherein the hydrophilic
resin comprises a polymer selected from polyoxaesters, hyaluronic
acids, and polyvinyl alcohols.
33. The adhesive structure of claim 25 wherein the polymer is a
biodegradable polymer selected from aliphatic polyesters, poly
(amino acids), copoly (ether-esters), polyalkylenes oxalates,
tyrosine-derived polycarbonates, poly (iminocarbonates),
polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters
containing amine groups, poly (anhydrides), polyphosphazenes,
collagen, elastin, hyaluronic acid, laminin, gelatin, keratin,
chondroitin sulfate, polyglycolide (PGA), poly(propylenefumarate),
polycyanoacrylate, polycaprolactone (PCL), poly(glycerol sebacate)
(PGS), poly(glycerol sebacate acrylate) (PGSA), and biodegradable
polyurethanes.
34. The adhesive structure of claim 25 wherein the polymer is a
non-biodegradable polymer selected from acrylics, polyamide-imide
(PAI), polyetherketones (PEEK), polycarbonate, polyethylenes (PE),
polybutylene terephthalates (PBT), polyethylene terephthalates
(PET), polypropylene, polyamide (PA), polyvinylidene fluoride
(PVDF), and polyvinylidene fluoride-co-hexafluoropropylene
(PVDF/HFP), polymethylmethacrylate (PMMA), polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate (PHEMA), poly(N-isopropylacrylamide)
(PNIPAAm) and polyolefins.
35. The adhesive structure of claim 21 wherein the surface is
substantially planar and the protrusions are within .+-.45 degrees
of normal to the planar surface.
36. The adhesive structure of claim 21 having a density of
protrusions on at least one of its surfaces ranging from about
1.times.10.sup.5 to about 6.times.10.sup.8 protrusions per
cm.sup.2.
37. The adhesive structure of claim 21 wherein at least a portion
of the adhesive structure has a dry adhesive strength of at least 3
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
38. The adhesive structure of claim 21 wherein at least a portion
of the adhesive structure has a wet adhesive strength of at least
0.5 N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
39. The adhesive structure of claim 25 wherein the polymer is
selected from at least one of poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), and polypropylene (PP)
and adhesion is measured by adhesive force measurements and ranges
from 0.1 to 0.5 N/cm.sup.2 on a target surface having a roughness
of 0.1 to 8 microns.
40. The adhesive structure of claim 21 which is at least partially
formed by a process selected from nanomolding using a template,
polymer self-assembly, lithography, and etching.
41. The adhesive structure of claim 21 wherein the two-sided
substrate comprises one or more extruded resin layers,
42. The adhesive structure of claim 41 wherein the two-sided
substrate comprises two or more co-extruded resin layers, each of
which resin layer can be the same as or different from another
resin layer of the substrate.
43. The adhesive structure of claim 41 wherein the two-sided
substrate is derived from a film co-extruded from more than one
resin.
44. The adhesive structure of claim 41 wherein the two-sided
substrate is selected from a single layer substrate comprising a
core layer, a double layer substrate comprising two skin layers,
and a triple layer substrate having a core layer and two skin
layers.
45. An adhesive structure comprising a surface from which extend
protrusions comprising a resin having a Young's modulus of greater
than 17 MPa, which protrusions are of sufficiently low diameter to
promote adhesion by increasing physical attractive forces, as
measured by shear adhesion between the adhesive structure and a
target surface, said adhesive structure further comprising chemical
groups on at least a portion of the adhesive structure surface,
capable of interacting with the target surface.
46. The adhesive structure of claim 45 wherein the chemical groups
are provided by cyanoacrylates, fibrin sealants,
hydroxysuccinimides, acrylates, and aldehydes.
47. The adhesive structure of claim 45 wherein the chemical groups
are provided by fibrin sealants.
48. The adhesive structure of claim 45 wherein the protrusions have
an average diameter ranging from 0.1 to 2 microns, an average
length greater than 3 microns and an aspect ratio (length/diameter)
of 2 to 30.
49. The adhesive structure of claim 45 wherein the structure is
integrally molded from a resin selected from at least one of
thermoplastic resin, thermosetting resin, and curable resin.
50. The adhesive structure of claim 45 wherein the resin comprises
at least one polymer having a Young's modulus of greater than 17
MPa.
51. The adhesive structure of claim 50 wherein the resin comprises
at least one polymer having a Young's modulus ranging from 20 MPa
to 5 GPa.
52. The adhesive structure of claim 50 wherein the polymer is
selected from at least one of a thermoplastic polymer.
53. The adhesive structure of claim 52 wherein the polymer is
selected from at least one of poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), and polypropylene
(PP).
54. The adhesive structure of claim 45 wherein the resin is
hydrophobic.
55. The adhesive structure of claim 54 wherein the hydrophobic
resin comprises a polymer selected from aliphatic polyesters, and
polypropylenes.
56. The adhesive structure of claim 45 wherein the resin is
hydrophilic.
57. The adhesive structure of claim 56 wherein the hydrophilic
resin comprises a polymer selected from polyoxaesters, hyaluronic
acids, and polyvinyl alcohols.
58. The adhesive structure of claim 50 wherein the polymer is a
biodegradable polymer selected from aliphatic polyesters, poly
(amino acids), copoly (ether-esters), polyalkylenes oxalates,
tyrosine-derived polycarbonates, poly (iminocarbonates),
polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters
containing amine groups, poly (anhydrides), polyphosphazenes,
collagen, elastin, hyaluronic acid, laminin, gelatin, keratin,
chondroitin sulfate, polyglycolide (PGA), poly(propylenefumarate),
polycyanoacrylate, polycaprolactone (PCL), poly(glycerol sebacate)
(PGS), poly(glycerol sebacate acrylate) (PGSA), and biodegradable
polyurethanes.
59. The adhesive structure of claim 50 wherein the polymer is a
non-biodegradable polymer selected from acrylics, polyamide-imide
(PAI), polyetherketones (PEEK), polycarbonate, polyethylenes (PE),
polybutylene terephthalates (PBT), polyethylene terephthalates
(PET), polypropylene, polyamide (PA), polyvinylidene fluoride
(PVDF), and polyvinylidene fluoride-co-hexafluoropropylene
(PVDF/HFP), polymethylmethacrylate (PMMA), polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate (PHEMA), poly(N-isopropylacrylamide)
(PNIPAAm) and polyolefins.
60. The adhesive structure of claim 45 wherein the surface is
substantially planar and the protrusions are within .+-.45 degrees
of normal to the planar surface.
61. The adhesive structure of claim 45 having a density of
protrusions on its surface ranging from about 1.times.10.sup.5 to
about 6.times.10.sup.8 protrusions per cm.sup.2.
62. The adhesive structure of claim 45 wherein at least a portion
of the adhesive structure has a dry adhesive strength of at least 3
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
63. The adhesive structure of claim 45 wherein at least a portion
of the adhesive structure has a wet adhesive strength of at least
0.5 N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
64. The adhesive structure of claim 50 wherein the polymer is
selected from at least one of poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), and polypropylene (PP)
and adhesion is measured by adhesive force measurements and ranges
from 0.1 to 0.5 N/cm.sup.2 on a target surface having a roughness
of 0.1 to 8 microns.
65. The adhesive structure of claim 1 which is at least partially
formed by a process selected from nanomolding using a template,
polymer self-assembly, lithography, and etching.
66. The adhesive structure of claim 45 which comprises a two-sided
substrate from each side of which extend the protrusions.
67. The adhesive structure of claim 66 wherein the two-sided
substrate comprises one or more extruded resin layers,
68. The adhesive structure of claim 66 wherein the two-sided
substrate comprises two or more co-extruded resin layers, each of
which resin layer can be the same as or different from another
resin layer of the substrate.
69. The adhesive structure of claim 66 wherein the two-sided
substrate is derived from a film co-extruded from more than one
resin.
70. The adhesive structure of claim 66 wherein the two-sided
substrate is selected from a single layer substrate comprising a
core layer, a double layer substrate comprising two skin layers,
and a triple layer substrate having a core layer and two skin
layers.
71. A method of providing an adhesive structure adherable to a
target surface which comprises: a) measuring surface roughness of
the target surface to determine the average longest dimension of
microstructures associated with the surface roughness; and b)
forming a polymer-containing adhesive structure comprising an
adhesive surface which includes protrusions of a sufficiently low
average diameter to interact with target microstructures on the
target surface to promote adhesion by increasing physical
attractive forces between the adhesive structure and the target
surface, as measured by shear adhesion.
72. The method of claim 71 wherein the polymer has a Young's
modulus above 17 MPa.
73. The adhesive structure of claim 71 wherein the target surface
comprises biological tissue.
74. The adhesive structure of claim 73 wherein the target surface
is selected from at least one of bladder tissue and intestinal
tissue.
75. A method for preparing an adhesive structure which comprises:
a) providing a specific solvent-dissolvable mold including
indentations; b) providing a meltable polymer having a Young's
modulus of greater than 17 MPa to the mold under conditions
sufficient to permit filling the indentations of the mold by the
polymer, said polymer being substantially non-dissolvable by the
specific solvent; c) treating the mold and polymer of step b) to an
extent sufficient to substantially solidify the polymer; and d)
exposing the mold and polymer to the specific solvent under
mold-dissolving conditions to provide a molded polymer substrate
material having a Young's modulus of greater than 17 MPa comprising
protrusions conforming to the indentations of the mold.
76. The method of claim 75 which further comprises at least one of
the following conditions: i) wherein the meltable polymer is
provided to the mold as a heat-softened film; ii) wherein the mold
comprises polycarbonate, the polymer is polydioxanone, and the
solvent is dichloromethane; iii) wherein step b) is carried out in
a first stage and second stage, wherein the second stage is carried
out at a greater pressure.
77. The method of claim 76 wherein the first stage is carried out
at a temperature ranging from 90 to 110.degree. C., pressure
ranging from 0 to 20 Bar, for a duration of 7 to 12 minutes, and
the second stage is carried out at a temperature ranging from 90 to
110.degree. C., pressure ranging from 6 to 20 Bar, for a duration
of 15 to 25 minutes.
78. The method of claim 77 wherein step b) provides a
solvent-dissolvable mold to both surfaces of the polymer film,
yielding a molded polymer substrate material comprising protrusions
extending from both sides of the film.
79. The method of claim 78 wherein step b)'s conditions sufficient
to permit filling the indentations of the mold by the polymer
include pressures provided by upper and lower horizontal opposing
surfaces, between which surfaces is positioned a space-filling shim
surrounding an opening in which are placed from the bottom 1) a
first solvent-dissolvable mold layer, 2) a meltable polymer layer,
and 3) a second solvent-dissolvable mold layer, and further
wherein, 4) an optional protective layer is provided between the
lower horizontal opposing surface and the first solvent-dissolvable
mold layer and 5) an optional protective layer is provided between
the upper horizontal opposing surface and the second
solvent-dissolvable mold layer.
80. A combination of an adhesive structure and a target to which
the adhesive structure is adherable, wherein the adhesive structure
comprises a surface from which extend substantially cylindrical
protrusions comprising a resin having a Young's modulus of greater
than 17 MPa, which protrusions are of sufficiently low average
diameter and sufficient average length to promote adhesion by Van
der Waals attractive forces between the adhesive structure and
target, as measured by shear adhesion.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to polymer-based structures
having shapes and mechanical properties that optimize adhesion to a
specific target, e.g., a tissue or organ target.
BACKGROUND OF THE INVENTION
[0002] There is an ongoing need for adhesive structures having
improved adhesion obtained through physical attractive forces. Such
structures can be suited to use in various applications, such as
medical applications, e.g., as an adjunct or replacement to sutures
and staples used to close surgical incisions. For the adhered to
substrate, e.g., living tissue, providing an adhesive structure
that provides adhesive forces by non-chemical interactions between
adhesive structure and substrate would be highly desirable.
[0003] Intermolecular forces are exerted by molecules on each other
and affect the macroscopic properties of the material of which the
molecules are a part. Such forces may be either attractive or
repulsive in nature. They are conveniently divided into two
classes: short-range forces, which operate when the centers of the
molecules are separated by 3 angstroms or less, and long-range
forces, which operate over greater distances.
[0004] Generally, if molecules do not interact chemically, the
short-range forces between them are repulsive. These forces arise
from interactions of the electrons associated with the molecules
and are also known as exchange forces. Molecules that interact
chemically have attractive exchange forces, also known as valence
forces. Mechanical rigidity of molecules and effects such as
limited compressibility of matter arise from repulsive exchange
forces.
[0005] For present purposes, physical attractive forces are
considered to be attractive forces that are not chemical in nature,
e.g., not dependent on or associated with ionic bonding, covalent
bonding, or hydrogen bonding. Physical attractive forces can
include long-range forces or van der Waals forces as they are also
called. These forces account for a wide range of physical
phenomena, such as friction, surface tension (capillary actions),
adhesion and cohesion of liquids and solids, viscosity and the
discrepancies between the actual behavior of gases and that
predicted by the ideal gas law. Typical bond energies from van der
Waals forces are about 1 kcal/mol compared to about 6 kcal/mol for
hydrogen bonds and about 80 kcal/mol for carbon-to-carbon bonds.
Van der Waals forces arise in a number of ways, one being the
tendency of electrically polarized molecules to become aligned.
Quantum theory indicates also that in some cases the electrostatic
fields associated with electrons in neighboring molecules constrain
the electrons to move more or less in phase.
[0006] The London dispersion force otherwise known as quantum
induced instantaneous polarization (one of the three types of van
der Waals forces) is caused by instantaneous changes in the dipole
of atoms, resulting from the location of the electrons in the
atoms' orbitals. When an electron is on one side of the nucleus,
this side becomes slightly negative (indicated by .delta.-); this
in turn repels electrons in neighboring atoms, making these regions
slightly positive (.delta.+). This induced dipole causes a brief
electrostatic attraction between the two molecules. The electron
immediately moves to another point and the electrostatic attraction
is broken. London dispersion forces are typically very weak because
the attractions are so quickly broken, and the charges involved are
so small.
[0007] Despite the weakness of van der Waals forces, it has been
recognized that such forces can contribute to adhesion by a
structure formed in nature. For example, it has been observed that
the adhesive force of a gecko's foot is attributable to the van der
Waals forces generated by hundreds of thousands of fibrillar,
hair-like microstructures known as setae, which terminate in even
smaller structures (200 to 400 nanometers in diameter) known as
spatulae. Such structure permits a gecko to climb even smooth
surfaces such as vertical planes of glass, achieving adhesion
without any requirement that the target substrate itself provide
adhesive characteristics. Structures mimicking a gecko's foot have
been attempted by various methods including nano-molding using a
template, polymer self-assembly, lithography, and etching. However,
such structures are inherently delicate and can suffer from
durability problems in practical applications. Accordingly,
structures offering adhesion attributable to van der Waals forces
but with simpler shapes and construction are desirable.
[0008] U.S. Pat. No. 6,872,439 proposes a fabricated microstructure
comprising at least one protrusion capable of providing an adhesive
force at a surface of between about 60 and 2,000 nano-Newtons. A
stalk supports the protrusion at an oblique angle relative to a
supporting surface, and the microstructure can adhere to different
surfaces.
[0009] U.S. Pat. No. 7,479,318 relates to a fibrillar
microstructure and processes for its manufacture. These processes
involve micromachining and molding, and can be used to prepare
sub-micron dimensioned fibrillar microstructures of any shape from
polymeric as well as other materials.
[0010] WO 2008076390 teaches dry adhesives and a method for forming
a dry adhesive structure on a substrate by forming a template
backing layer of energy sensitive material on the substrate,
forming a template layer of energy sensitive material on the
template backing layer, exposing the template layer to a
predetermined pattern of energy, removing a portion of the template
layer exposed to the predetermined pattern of energy, and leaving a
template structure formed from energy sensitive material and
connected to the substrate through the template backing layer.
[0011] WO 2009067482 proposes an adhesive article that includes a
biocompatible and at least partially biodegradable substrate having
a surface; and a plurality of protrusions extending from the
surface. The protrusions include a biocompatible and at least
partially biodegradable material, and have an average height of
less than approximately 1,000 micrometers.
[0012] A review of the prior art shows use of micro-nano structures
on polymer substrates for adhesion to tissue (WO 2009067482), but
the materials used to fabricate these structures comprise "softer"
polymers, i.e., polymers or polymer mixtures having a Young's
modulus .ltoreq.17 MPa. Moreover, they do not provide a solution
for adhesion to specific types of tissue.
[0013] It would be desirable to provide an adhesive structure
without relying solely on surface chemical groups to provide
acceptable conformal contact and adhesion with its intended target
surface.
[0014] It would also be desirable to provide an adhesive structure
that has a stiffness (Young's modulus) greater than 17 MPa that
provides a means by which a fluid such as the tissue's own fluid or
a chemical group such as a fibrin sealant can wick into the
structure to enhance adhesion with its intended target surface.
SUMMARY OF THE INVENTION
[0015] The present invention relates to polymer-based, adhesive
micro-nano structures with formed surface features and mechanical
properties that optimize adhesion to a specific target. The present
invention relates to structures containing pillar-like projections
which can be of a specific diameter, length, and aspect ratio
(length/diameter) or spacing and can be fabricated with stiff
polymers. The shape of the structure can be formed to enhance
adhesion to specific substrates, e.g., certain tissue types.
Suitable polymers for use in the present invention include stiff
polymers having Young's modulus >17 MPa that can be hydrophilic
or hydrophobic, or bio-absorbable or non bio-absorbable, depending
on their intended use and target substrate.
[0016] In one aspect, the present invention relates to an adhesive
structure comprising a substrate with a surface from which extend
protrusions, e.g., substantially cylindrical protrusions,
comprising a resin having a Young's modulus of greater than 17 MPa,
as measured by ASTM standard D412-98a, which protrusions are of
sufficiently low average diameter to promote adhesion by increasing
physical attractive forces, e.g., van der Waals attractive forces,
between the adhesive structure and a target surface to which the
adhesive structure is to be adhered, as measured by shear adhesion.
For present purposes, a resin can be defined as any of a class of
solid or semisolid viscous substances obtained either as exudations
from certain plants or prepared by polymerization of simpler
molecules. Resins can include single polymer compounds or mixtures
of polymer compounds.
[0017] For purposes of the present invention, a target surface can
include biological tissue, or non-tissue, e.g., a surface
associated with a medical device. In certain embodiments, the
target surface can be associated with the adhesive structure
itself, e.g., in the case of a substrate or film comprising
protrusions on either side, which can be utilized as a double-sided
adhesive tape. Such double-sided embodiments can even be wrapped
around itself or a similar adhesive structure, to provide adhesion
at least partially promoted by physical attractive forces.
[0018] In still another aspect, the present invention relates to an
adhesive structure comprising a two-sided substrate from each side
of which extend protrusions comprising one or more resins having a
Young's modulus of greater than 17 MPa, which protrusions are of
sufficiently low diameter to promote adhesion by increasing
physical attractive forces, as measured by shear adhesion between
the adhesive structure and a target surface.
[0019] In another aspect, the present invention relates to an
adhesive structure comprising a substrate with a surface from which
extend protrusions, e.g., substantially cylindrical protrusions,
comprising a resin having a Young's modulus of greater than 17 MPa,
as measured by ASTM standard D412-98a, which protrusions are of
sufficiently low average diameter to promote adhesion by increasing
physical attractive forces between the adhesive structure and a
target surface to which the adhesive structure is to be adhered, as
measured by shear adhesion, wherein the substrate surface contains
reactive chemical groups that interact with the target surface.
[0020] In another aspect, the present invention relates to a method
for providing an adhesive structure adherable to a target surface
which comprises: a) measuring surface roughness of the target
surface to determine average dimensions of microstructures
associated with the surface; and b) forming a polymer-containing
adhesive structure comprising a substrate having an adhesive
surface which includes protrusions, e.g., pillar-like protrusions,
of sufficient height, diameter, and aspect ratio for the surface to
interact with the microstructures on the target surface to promote
adhesion by van der Waals attractive forces between the adhesive
structure and the target surface, as measured by shear adhesion.
For present purposes, microstructures include micron-dimensioned
and sub-micron-dimensioned structures, e.g., nano-dimensioned
structures, of any shape, e.g., fibrillar microstructures or
pillar-like microstructures, whose lengths (or heights) typically
exceed their diameters.
[0021] In still another aspect, the present invention relates to a
method of providing an adhesive structure adherable to a target
surface which comprises: a) measuring surface roughness of the
target surface to determine the average longest dimension of
microstructures associated with the surface roughness; b) forming a
polymer-containing adhesive structure comprising an adhesive
surface which includes protrusions of a sufficiently low average
diameter to interact with target microstructures on the target
surface to promote adhesion by physical attractive forces, e.g.,
Van der Waals attractive forces, between the adhesive structure and
the target surface, as measured by shear adhesion.
[0022] In yet another aspect, the present invention relates to a
method for preparing an adhesive structure which comprises: a)
providing a specific solvent-dissolvable mold including
indentations; b) introducing a stiff polymer having a Young's
modulus of greater than 17 MPa or a precursor to the stiff polymer,
to the mold under conditions, e.g., temperatures and pressures,
sufficient to permit filling the indentations of the mold by the
polymer, said polymer being substantially non-dissolvable by the
specific solvent; c) cooling the mold and polymer of step b) to an
extent sufficient to substantially solidify the polymer; d)
releasing pressure on the mold and polymer of step c); and e)
exposing the mold and polymer to the specific solvent under
mold-dissolving conditions to provide a molded polymer substrate
material having a Young's modulus of greater than 17 MPa comprising
protrusions conforming to the indentations of the mold. In certain
embodiments of the invention, the stiff polymer can be provided as
a meltable polymer. In some embodiments the stiff polymer can be
provided as a soluble polymer, i.e., a polymer which can be
provided dissolved in a "non-specific solvent," hereinafter
defined. In some embodiments, introducing a stiff polymer having a
Young's modulus of greater than 17 MPa to the mold can be carried
out by providing monomer precursors which can be polymerized within
the mold. In other embodiments of the invention, introducing a
stiff polymer having a Young's modulus of greater than 17 MPa to
the mold can be carried out by providing a precursor polymer
mixture comprising soluble polymer and non-specific solvent, or
comprising soluble polymer precursors and non-specific solvent,
into the mold and evaporating off the non-specific solvent. By
"non-specific solvent" is meant a solvent which will dissolve the
ultimate stiff polymer product or its precursors, without
substantially dissolving the "specific solvent dissolvable
mold."
[0023] In another aspect, the present invention relates to a method
for preparing an adhesive structure which comprises: a) providing a
specific solvent-dissolvable mold including indentations; b)
providing to the mold a polymer in a mold-conformable condition
having a Young's modulus of greater than 17 MPa under conditions
sufficient to permit filling the indentations of the mold by the
polymer, said polymer being substantially non-dissolvable by the
specific solvent; c) treating the mold and polymer of step b) to an
extent sufficient to substantially solidify the polymer; and d)
exposing the mold and polymer to the specific solvent under
mold-dissolving conditions to provide a molded polymer substrate
material having a Young's modulus of greater than 17 MPa comprising
protrusions conforming to the indentations of the mold.
[0024] In still another aspect, the present invention relates to a
combination of an adhesive structure and a target to which the
adhesive structure is adherable, wherein the adhesive structure
comprises a surface from which extend substantially cylindrical
protrusions comprising a resin having a Young's modulus of greater
than 17 MPa, which protrusions are of sufficiently low average
diameter and sufficient average length to promote adhesion by Van
der Waals attractive forces between the adhesive structure and
target, as measured by shear adhesion.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 is a scanning electron microscope image of a
polypropylene substrate with micropillars of 1 micron
diameter.times.20 microns length.
[0026] FIG. 2 presents shear adhesion forces (adhesive forces)
between polypropylene substrates with pillar-like extensions of 1
micron diameter and 20 microns length and target substrates of
varying surface roughness values--flat glass, 3 mcirons, 8 microns,
and 18 microns, under wet conditions i.e. when immersed in a water
bath.
[0027] FIG. 3 depicts shear adhesion force (10.sup.4 N/m.sup.2)
comparisons for polypropylene substrates with pillar-like
extensions of 1 micron diameter and 20 micron length and target
substrates against flat PP film and two tissue types--intestine and
bladder.
[0028] FIG. 4 is a photograph depicting a sample holder apparatus
used to hold tissue samples when measuring shear adhesion of
polymer samples to freshly harvested tissue on a mechanical testing
set-up.
[0029] FIG. 5 is a photograph depicting a sample holder apparatus
for a tissue sample mounted on a mechanical tester for measuring
shear adhesion of polymer samples to freshly harvested tissue.
[0030] FIG. 6 depicts adhesion strength for a polypropylene
substrate of the present invention having pillars of about one
micron diameter and about 20 microns in length against three
different tissue types--intestine, bladder, and epithelium.
[0031] FIG. 7 depicts the effect of pillar dimensions of
polypropylene substrates having respective pillar dimensions of
about 0.6 micron diameter.times.about 20 microns lengths and 5
microns diameter.times.about 15 microns lengths when tested against
two tissue types, intestine and epithelium.
[0032] FIG. 8 depicts a SEM image of a polypropylene tape with
adhesive features on both sides.
[0033] FIG. 9 depicts the comparison of the burst pressure data for
a flat PP film and the double sided PP tape on a porcine
intestine.
[0034] FIG. 10 is a scanning electron microscope image of the
DL-PLA substrate comprising 200 nm diameter.times.2 microns height
nanopillars.
[0035] FIG. 11 depicts shear adhesion forces for pillar-like
protrusions (0.2 micron diameter and 2 microns length) for PLA as
well as its corresponding flat surface film (unpillared), against
substrates with varying surface roughness values--flat glass, 0.1
micron, 0.5 micron, 3 microns, and 8 microns.
DETAILED DESCRIPTION
[0036] Young's modulus (E) is a measure of the stiffness of an
isotropic elastic material. It is also known as the Young modulus,
modulus of elasticity, elastic modulus (though Young's modulus is
actually one of several elastic moduli such as the bulk modulus and
the shear modulus) or tensile modulus. It is defined as the ratio
of the uniaxial stress over the uniaxial strain in the range of
stress in which Hooke's Law holds. This can be experimentally
determined from the slope of a stress-strain curve created during
tensile tests conducted on a sample of the material. Young's
modulus quantifies the elasticity of the polymer. It is defined,
for small strains, as the ratio of rate of change of stress to
strain. Like tensile strength, this is highly relevant in polymer
applications involving the physical properties of polymers, such as
rubber bands. The modulus is strongly dependent on temperature.
[0037] Young's modulus, E, can be calculated by dividing the
tensile stress by the tensile strain:
E .ident. tensile stress tensile strain = .sigma. = F / A 0 .DELTA.
L / L 0 = FL 0 A 0 .DELTA. L ##EQU00001##
where
[0038] E is the Young's modulus (modulus of elasticity)
[0039] F is the force applied to the object;
[0040] A.sub.0 is the original cross-sectional area through which
the force is applied;
[0041] .DELTA.L is the amount by which the length of the object
changes;
[0042] L.sub.0 is the original length of the object.
[0043] For present purposes, Young's modulus can be measured in
accordance with ASTM standard D412-98a.
[0044] For present purposes, target surface roughness can be
defined as the average longest dimension of the particles or
microstructures that provide roughness to a surface of the target.
For a spherical or roughly spherical shape, the diameter can be
considered the longest dimension. Standard surface roughness
analysis can be carried out by microscopy techniques such as
scanning electron microscopy (SEM), atomic force microscopy (AFM)
and optical interferometric profiling. Another method of
determining roughness is by comparison of a surface with silicon
carbide grinding papers of different FEPA (Federation of European
Producers Association) surface roughnesses--P#4000 (3 microns size
grains), P#2400 (8 microns size grains) and P#500 (30 microns size
grains). These grains are roughly spherical and their size
determined by their largest dimension.
[0045] For purposes of the present invention, a target surface can
include biological tissue, or non-tissue, e.g., a surface
associated with a medical device or prosthetic. In certain
embodiments, the target surface can be associated with the adhesive
structure itself, e.g., in the case of a substrate or film
comprising protrusions on either side, which can be utilized as a
double-sided adhesive tape. Such a double-sided embodiment can even
be wrapped around itself or a similar adhesive structure, to
provide adhesion at least partially promoted by physical attractive
forces.
[0046] The polymer substrates of which the structures are made are
typically stiff, with a Young's modulus greater than 17 MPa, and
can be hydrophilic or hydrophobic. The dimensions of the
nanostructures are engineered for adhesion to specific targets with
a diameter from 0.1-5 microns and height greater than 1 micron. The
dimensions are tailored to match the dimensions of the substrate so
that maximum adhesion can be had. Polymers used may be biodurable
such as polypropylene (PP) or bioabsorbable such as
poly(lactic-co-glycolic acid) (PLGA) and polydioxanone (PDO).
[0047] As earlier noted, in one aspect the present invention
relates to an adhesive structure comprising a surface from which
extend protrusions comprising a resin having a Young's modulus of
greater than 17 MPa, which protrusions are of sufficiently low
diameter to promote adhesion by increasing physical attractive
forces, e.g., Van der Waals attractive forces between the adhesive
structure and a target surface, as measured by shear adhesion.
[0048] In one embodiment, the protrusions have an average diameter
ranging from 0.2 to 5 microns, an average length greater than 1
micron and an aspect ratio (length/diameter) of 1 to 33
[0049] In another embodiment, the protrusions have an average
diameter ranging from 0.2 to 2 microns, an average length greater
than 3 microns and an aspect ratio (length/diameter) of 2 to
30.
[0050] In still another embodiment, the structure is integrally
molded from a resin selected from at least one of thermoplastic
resin, thermosetting resin, and curable resin. By integrally molded
is meant that the structure is formed in one piece, including its
protrusions, from a mold. For present purposes, thermoplastic resin
is a resin that softens when heated and hardens again when cooled.
Thermosetting resin is a resin that hardens when heated, cannot be
remolded and is deformable from a solid to a liquid. Curable resins
are resins that are toughened or hardened by cross-linking of their
polymer chains, brought about by chemical additives, ultraviolet
radiation, electron beam, and/or heat.
[0051] In yet another embodiment, the resin comprises at least one
polymer having a Young's modulus of greater than 17 MPa.
[0052] In still yet another embodiment, the resin comprises at
least one polymer having a Young's modulus ranging from 20 MPa to 5
GPa.
[0053] In yet still another embodiment, the polymer is selected
from at least one of a thermoplastic polymer. For present purposes,
thermoplastic polymer is a polymer that softens when heated and
hardens again when cooled.
[0054] In another embodiment, the polymer is selected from at least
one of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA),
polydioxanone (PDO), poly(trimethylene carbonate),
poly(caprolactone-co-glycolide) and polypropylene (PP).
[0055] In still another embodiment, the resin is hydrophobic. For
present purposes, a hydrophobic resin is a resin that does not
substantially absorb, or be wetted by, water.
[0056] In yet another embodiment, the resin is hydrophobic and
comprises a polymer selected from aliphatic polyesters, and
polypropylenes.
[0057] In still yet another embodiment, the resin is hydrophilic.
For present purposes, hydrophilic resins are resins that have a
Young's modulus greater than 17 MPa and can be generally classified
by their interaction with water into roughly two types,
water-soluble resins and water-absorbent resins. Water-soluble
resins are hydrophilic resins of the type which dissolve in water
and are used, for example, as water treatment grade flocculants,
oil drilling additives, food additives, and viscosity enhancers.
Absorbent resins are water-insoluble hydrophilic resins of the type
which absorb water and consequently undergo gelation and are widely
used in the fields of agriculture and forestry and in the field of
civil engineering as well as in the field of hygienic materials
such as disposable diapers and sanitary napkins. In yet still
another embodiment, the hydrophilic resin comprises a polymer
selected from polyoxaesters, hyaluronic acids, and polyvinyl
alcohols.
[0058] In another embodiment, the polymer is a biodegradable
polymer. For present purposes, a biodegradable polymer is a polymer
capable of being decomposed by the action of biological agents,
e.g., bacteria, enzymes or water.
[0059] In still another embodiment, the polymer is a biodegradable
polymer selected from aliphatic polyesters, poly (amino acids),
copoly (ether-esters), polyalkylenes oxalates, tyrosine-derived
polycarbonates, poly (iminocarbonates), polyorthoesters,
polyoxaesters, polyamidoesters, polyoxaesters containing amine
groups, poly (anhydrides), polyphosphazenes, collagen, elastin,
hyaluronic acid, laminin, gelatin, keratin, chondroitin sulfate,
polyglycolide (PGA), poly(propylenefumarate), poly(cyanoacrylate),
polycaprolactone (PCL), poly(trimethylene carbonate),
poly(lactide), poly(dioxanone), poly(glycerol sebacate) (PGS),
poly(glycerol sebacate acrylate) (PGSA), and biodegradable
polyurethanes.
[0060] In yet another embodiment, the polymer is a
non-biodegradable polymer. For present purposes, a
non-biodegradable polymer is a polymer that is not capable of being
decomposed by the action of biological agents, e.g., bacteria,
enzymes, or water.
[0061] In still yet another embodiment, the polymer is a
non-biodegradable polymer selected from acrylics, polyamide-imide
(PAI), polyetherketones (PEEK), polycarbonate, polyethylenes (PE),
polybutylene terephthalates (PBT), polyethylene terephthalates
(PET), polypropylene, polyamide (PA), polyvinylidene fluoride
(PVDF), and polyvinylidene fluoride-co-hexafluoropropylene
(PVDF/HFP), polymethylmethacrylate (PMMA), polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate, polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate (PHEMA), poly(N-isopropylacrylamide)
(PNIPAAm), and polyolefins.
[0062] In yet still another embodiment, the adhesive structure
surface is substantially planar and the protrusions are within
.+-.45 degrees of normal to the planar surface.
[0063] In still yet another embodiment, the adhesive structure
surface is substantially planar and the protrusions are within
.+-.30 degrees of normal to the planar surface
[0064] In another embodiment, the adhesive structure has a
protrusion density of from 1.times.10.sup.5 to 6.times.10.sup.8
protrusions/cm.sup.2. For present purposes, "protrusion density"
can be described as the number of protrusions or pillars present
per square centimeter of adhesive structure surface.
[0065] In still another embodiment, the adhesive structure has a
density of protrusions on its surface ranging from about
10.times.10.sup.6 to about 50.times.10.sup.6 protrusions per
cm.sup.2.
[0066] In yet another embodiment, at least a portion of the
adhesive structure has a dry adhesive strength of at least 3
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
[0067] In still yet another embodiment, at least a portion of the
adhesive structure has a wet adhesive strength of at least 0.5
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
[0068] In yet still another embodiment, the polymer is selected
from at least one of poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), poly(glycolide),
poly(trimethylene carbonate), poly(glycolide) and polypropylene
(PP) and adhesion is measured by adhesive force measurements and
ranges from 0.1 to 0.5 N/cm.sup.2 on a target surface having a
roughness of 0.1 to 8 microns.
[0069] In another embodiment, the adhesive structure is at least
partially formed by a process selected from nanomolding using a
template, polymer self-assembly, lithography, and etching.
[0070] As earlier noted, in another aspect the present invention
relates to an adhesive structure comprising a two-sided substrate
from each side of which extend protrusions comprising one or more
resins having a Young's modulus of greater than 17 MPa, which
protrusions are of sufficiently low diameter to promote adhesion by
increasing physical attractive forces between the adhesive
structure and a target surface, as measured by shear adhesion.
[0071] In one embodiment of this aspect, the protrusions have an
average diameter ranging from 0.2 to 5 microns, an average length
greater than 1 micron and an aspect ratio (length/diameter) of 1 to
33.
[0072] In another embodiment, the protrusions have an average
diameter ranging from 0.2 to 2 microns, an average length greater
than 3 microns and an aspect ratio (length/diameter) of 2 to
30.
[0073] In still another embodiment, the structure is integrally
molded from a resin selected from at least one of thermoplastic
resin, thermosetting resin, and curable resin.
[0074] In yet another embodiment, the resin comprises at least one
polymer having a Young's modulus of greater than 17 MPa.
[0075] In still yet another embodiment, the resin comprises at
least one polymer having a Young's modulus ranging from 20 MPa to 5
GPa.
[0076] In yet still another embodiment, the polymer is selected
from at least one of a thermoplastic polymer.
[0077] In another embodiment, the polymer is selected from at least
one of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA),
polydioxanone (PDO), poly(trimethylene carbonate),
poly(caprolactone-co-glycolide) and polypropylene (PP).
[0078] In still another embodiment, the resin is hydrophobic.
[0079] In yet another embodiment, the resin is hydrophobic and
comprises a polymer selected from aliphatic polyesters, and
polypropylenes.
[0080] In still yet another embodiment, the resin is
hydrophilic.
[0081] In yet still another embodiment, the hydrophilic resin
comprises a polymer selected from polyoxaesters, hyaluronic acids,
and polyvinyl alcohols.
[0082] In another embodiment, the polymer is a biodegradable
polymer.
[0083] In still another embodiment, the polymer is a biodegradable
polymer selected from aliphatic polyesters, poly (amino acids),
copoly (ether-esters), polyalkylenes oxalates, tyrosine-derived
polycarbonates, poly (iminocarbonates), polyorthoesters,
polyoxaesters, polyamidoesters, polyoxaesters containing amine
groups, poly (anhydrides), polyphosphazenes, collagen, elastin,
hyaluronic acid, laminin, gelatin, keratin, chondroitin sulfate,
polyglycolide (PGA), poly(propylenefumarate), poly(cyanoacrylate),
polycaprolactone (PCL), poly(trimethylene carbonate),
poly(lactide), poly(dioxanone), poly(glycerol sebacate) (PGS),
poly(glycerol sebacate acrylate) (PGSA), and biodegradable
polyurethanes.
[0084] In yet another embodiment, the polymer is a
non-biodegradable polymer.
[0085] In still yet another embodiment, the polymer is a
non-biodegradable polymer selected from acrylics, polyamide-imide
(PAI), polyetherketones (PEEK), polycarbonate, polyethylenes (PE),
polybutylene terephthalates (PBT), polyethylene terephthalates
(PET), polypropylene, polyamide (PA), polyvinylidene fluoride
(PVDF), and polyvinylidene fluoride-co-hexafluoropropylene
(PVDF/HFP), polymethylmethacrylate (PMMA), polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate, polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate (PHEMA), poly(N-isopropylacrylamide)
(PNIPAAm), and polyolefins.
[0086] In yet still another embodiment, the adhesive structure
surface is substantially planar and the protrusions are within
.+-.45 degrees of normal to the planar surface.
[0087] In another embodiment, the adhesive structure has a
protrusion density of from 1.times.10.sup.5 to 6.times.10.sup.8
protrusions/cm.sup.2.
[0088] In yet another embodiment, at least a portion of the
adhesive structure has a dry adhesive strength of at least 3
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
[0089] In still yet another embodiment, at least a portion of the
adhesive structure has a wet adhesive strength of at least 0.5
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
[0090] In yet still another embodiment, the polymer is selected
from at least one of poly(Iactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), poly(glycolide),
poly(trimethylene carbonate), poly(glycolide) and polypropylene
(PP) and adhesion is measured by adhesive force measurements and
ranges from 0.1 to 0.5 N/cm.sup.2 on a target surface having a
roughness of 0.1 to 8 microns.
[0091] In another embodiment, the adhesive structure is at least
partially formed by a process selected from nanomolding using a
template, polymer self-assembly, lithography, and etching.
[0092] In yet another embodiment, the two-sided substrate comprises
one or more extruded resin layers.
[0093] In still another embodiment, the adhesive structure
two-sided substrate comprises two or more co-extruded resin layers,
each of which resin layer can be the same as or different from
another resin layer of the substrate.
[0094] In still yet another embodiment, the two-sided substrate is
derived from a film co-extruded from more than one resin.
[0095] In yet still another embodiment, the two-sided substrate is
selected from a single layer substrate comprising a core layer, a
double layer substrate comprising two skin layers, and a triple
layer substrate having a core layer and two skin layers.
[0096] As earlier noted, in another aspect, the present invention
relates to an adhesive structure comprising a surface from which
extend protrusions comprising a resin having a Young's modulus of
greater than 17 MPa, which protrusions are of sufficiently low
diameter to promote adhesion by increasing physical attractive
forces, as measured by shear adhesion, between the adhesive
structure and a target surface, said adhesive structure further
comprising chemical groups on at least a portion of the adhesive
structure surface, capable of interacting with the target
surface.
[0097] In an embodiment of this aspect of the invention, the
chemical groups are provided by cyanoacrylates, fibrin sealants,
hydroxysuccinimides, acrylates, and aldehydes.
[0098] In another embodiment of this aspect of the invention, the
chemical groups are provided by fibrin sealants.
[0099] In another embodiment, the protrusions have an average
diameter ranging from 0.2 to 2 microns, an average length greater
than 3 microns and an aspect ratio (length/diameter) of 2 to
30.
[0100] In still another embodiment, the structure is integrally
molded from a resin selected from at least one of thermoplastic
resin, thermosetting resin, and curable resin.
[0101] In yet another embodiment, the resin comprises at least one
polymer having a Young's modulus of greater than 17 MPa.
[0102] In still yet another embodiment, the resin comprises at
least one polymer having a Young's modulus ranging from 20 MPa to 5
GPa.
[0103] In yet still another embodiment, the polymer is selected
from at least one of a thermoplastic polymer.
[0104] In another embodiment, the polymer is selected from at least
one of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA),
polydioxanone (PDO), poly(trimethylene carbonate),
poly(caprolactone-co-glycolide) and polypropylene (PP).
[0105] In still another embodiment, the resin is hydrophobic.
[0106] In yet another embodiment, the resin is hydrophobic and
comprises a polymer selected from aliphatic polyesters, and
polypropylenes.
[0107] In still yet another embodiment, the resin is
hydrophilic.
[0108] In yet still another embodiment, the hydrophilic resin
comprises a polymer selected from polyoxaesters, hyaluronic acids,
and polyvinyl alcohols.
[0109] In still another embodiment, the polymer is a biodegradable
polymer selected from aliphatic polyesters, poly (amino acids),
copoly(ether-esters), polyalkylenes oxalates, tyrosine-derived
polycarbonates, poly (iminocarbonates), polyorthoesters,
polyoxaesters, polyamidoesters, polyoxaesters containing amine
groups, poly (anhydrides), polyphosphazenes, collagen, elastin,
hyaluronic acid, laminin, gelatin, keratin, chondroitin sulfate,
polyglycolide (PGA), poly(propylenefumarate), poly(cyanoacrylate),
polycaprolactone (PCL), poly(trimethylene carbonate),
poly(lactide), poly(dioxanone), poly(glycerol sebacate) (PGS),
poly(glycerol sebacate acrylate) (PGSA), and biodegradable
polyurethanes.
[0110] In still yet another embodiment, the polymer is a
non-biodegradable polymer selected from acrylics, polyamide-imide
(PAI), polyetherketones (PEEK), polycarbonate, polyethylenes (PE),
polybutylene terephthalates (PBT), polyethylene terephthalates
(PET), polypropylene, polyamide (PA), polyvinylidene fluoride
(PVDF), and polyvinylidene fluoride-co-hexafluoropropylene
(PVDF/HFP), polymethylmethacrylate (PMMA), polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate, polyvinylalcohol (PVA),
polyhydroxyethylmethacrylate (PHEMA), poly(N-isopropylacrylamide)
(PNIPAAm), and polyolefins.
[0111] In yet still another embodiment, the adhesive structure
surface is substantially planar and the protrusions are within
.+-.45 degrees of normal to the planar surface.
[0112] In another embodiment, the adhesive structure has a
protrusion density of from 1.times.10.sup.5 to 6.times.10.sup.8
protrusions/cm.sup.2.
[0113] In yet another embodiment, at least a portion of the
adhesive structure has a dry adhesive strength of at least 3
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
[0114] In still yet another embodiment, at least a portion of the
adhesive structure has a wet adhesive strength of at least 0.5
N/cm.sup.2 of projected area when measured according to ASTM
standard D4501.
[0115] In yet still another embodiment, the polymer is selected
from at least one of poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), polydioxanone (PDO), poly(glycolide),
poly(trimethylene carbonate), poly(glycolide) and polypropylene
(PP) and adhesion is measured by adhesive force measurements and
ranges from 0.1 to 0.5 N/cm.sup.2 on a target surface having a
roughness of 0.1 to 8 microns.
[0116] In another embodiment, the adhesive structure is at least
partially formed by a process selected from nanomolding using a
template, polymer self-assembly, lithography, and etching.
[0117] In still another embodiment, the adhesive structure
comprises a two-sided substrate from each side of which extend the
protrusions.
[0118] In yet another embodiment, the two-sided substrate comprises
one or more extruded resin layers.
[0119] In still another embodiment, the two-sided substrate
comprises two or more co-extruded resin layers, each of which resin
layer can be the same as or different from another resin layer of
the substrate.
[0120] In still yet another embodiment, the two-sided substrate is
derived from a film co-extruded from more than one resin.
[0121] In yet still another embodiment, the two-sided substrate is
selected from a single layer substrate comprising a core layer, a
double layer substrate comprising two skin layers, and a triple
layer substrate having a core layer and two skin layers.
[0122] In another embodiment of this aspect, the chemical groups
are selected from pressure sensitive adhesives such as acrylates,
adhesives applied in the molten state (hot melt adhesives), solvent
based adhesives such as poly(vinyl acetate), multi-part adhesives
that can be cured by radiation, heat or moisture such as
cyanoacrylates, and urethanes, natural sealants such as fibrin
sealants and starches, hydroxysuccinimides, and aldehydes.
[0123] As earlier noted, another aspect of the invention is
directed to a method of providing an adhesive structure adherable
to a target surface which comprises: a) measuring surface roughness
of the target surface to determine the average longest dimension of
microstructures associated with the surface roughness; and b)
forming a polymer-containing adhesive structure comprising an
adhesive surface which includes protrusions of a sufficiently low
average diameter to interact with target microstructures on the
target surface to promote adhesion by increasing physical
attractive forces between the adhesive structure and the target
surface, as measured by shear adhesion.
[0124] In one embodiment, the polymer has a Young's modulus above
17 MPa.
[0125] In another embodiment, the target surface comprises
biological tissue.
[0126] In still another embodiment, the target surface is selected
from at least one of bladder tissue and intestinal tissue.
[0127] As earlier noted, yet another aspect of the invention
relates to a method for preparing an adhesive structure which
comprises: a) providing a specific solvent-dissolvable mold
including indentations; b) providing a meltable polymer having a
Young's modulus of greater than 17 MPa to the mold under conditions
sufficient to permit filling the indentations of the mold by the
polymer, said polymer being substantially non-dissolvable by the
specific solvent; c) treating the mold and polymer of step b) to an
extent sufficient to substantially solidify the polymer; and d)
exposing the mold and polymer to the specific solvent under
mold-dissolving conditions to provide a molded polymer substrate
material having a Young's modulus of greater than 17 MPa comprising
protrusions conforming to the indentations of the mold. Optionally,
this aspect further comprises at least one of the following
conditions: [0128] i) wherein the meltable polymer is provided to
the mold as a softened film; [0129] ii) wherein the mold comprises
polycarbonate, the polymer is thermoplastic, meltable polymer,
e.g., polydioxanone and the solvent is dichloromethane; and [0130]
iii) wherein step b) is carried out in a first stage and second
stage, wherein the second stage is carried out at a greater
pressure.
[0131] For present purposes, a meltable polymer can include a
single polymer or a mixture of polymers.
[0132] In one embodiment, the first stage is carried out at a
temperature ranging from 90 to 110.degree. C., pressure ranging
from about 0 to about 20 kPa (about 0 to about 20 Bar), for a
duration of 7 to 12 minutes, and the second stage is carried out at
a temperature ranging from 90 to 110.degree. C., pressure ranging
from about 6 to about 20 kPa (about 6 to about 20 Bar), for a
duration of 15 to 25 minutes.
[0133] In another embodiment of this aspect, step b) provides a
solvent-dissolvable mold to both surfaces of the meltable polymer
film, yielding a molded polymer substrate material comprising
substantially cylindrical protrusions extending from both sides of
the film.
[0134] In another embodiment of this aspect of the invention, step
b) provides a solvent-dissolvable mold to both surfaces of the
polymer film, yielding a molded polymer substrate material
comprising protrusions extending from both sides of the film.
[0135] In yet another embodiment, step b)'s conditions are
sufficient to permit filling the indentations of the mold by the
polymer and include pressures provided by upper and lower
horizontal opposing surfaces, between which surfaces is positioned
a space-filling shim surrounding an opening in which are placed
from the bottom 1) a first solvent-dissolvable mold layer, 2) a
meltable polymer layer, and 3) a second solvent-dissolvable mold
layer, and further wherein, 4) an optional protective layer is
provided between the lower horizontal opposing surface and the
first solvent-dissolvable mold layer and 5) an optional protective
layer is provided between the upper horizontal opposing surface and
the second solvent-dissolvable mold layer.
[0136] The invention is further explained in the description that
follows with reference to the drawings illustrating, by way of
non-limiting examples, various embodiments of the invention.
Example 1
[0137] The aim of this example was to fabricate polypropylene films
with pillar like protrusions. A commercial track etched
polycarbonate membrane was obtained from Millipore Corporation of
Billerica, Mass., USA having pores of 0.6 microns diameter and a
circular diameter of 2.5 cm, with a thickness of 20 microns. The
membrane was used as a template to imprint a solvent-resistant
polypropylene (PP) polymer film of 300 microns thickness, obtained
from Ethicon, Inc. of Somerville, N.J., USA. The polypropylene film
was pressed into the polycarbonate membrane template under
controlled temperature and pressures (180.degree. C., 600 kPa (6
bar)) for 20 minutes, melting the polypropylene and forming an
overfilling of polypropylene to the top side of the membrane. The
polypropylene polymer and the membrane are cooled to 175.degree. C.
before removal of pressure, after which the polymer structures are
de-molded and released by dissolving the membrane in
dichloromethane. The overfilling of polypropylene holds the
resulting pillar-like structures in place in the subsequent removal
of the membrane by dissolving with dicholoromethane. After the
membrane was completely dissolved and dried, the substrate was
exposed to oxygen plasma to etch the overfilled layer of polymer on
top, thereby releasing the pillar-like structures. FIG. 1 depicts a
scanning electron microscope image of the resulting polypropylene
substrate with micropillars (substantially cylindrical protrusions)
of 0.6 microns diameter.times.20 microns length.
Example 2
[0138] The aim of this example was to develop an accurate and
reproducible test method to measure shear adhesion. Modifications
were made to the mechanical testing instrument sold under the
tradename INSTRON by Instron Industrial Products, Grove City, Pa.
The mechanical testing set up was modified to improve the precision
and reproducibility of the shear adhesion measurements of the films
having pillar-like structures. The modifications were made to
decrease the source of noise from the hardware components and
control the preload or initial contact force between the adhesive
surfaces. The standard clamp operated with compressed air to grip
the glass slide was replaced by a fixed rigid clamp and the length
of the glass slide was shortened to reduce noise due to cantilever
bending effect. Similarly, the length of the lower glass slide was
shortened to reduce noise. A solid block of aluminum was used as a
backing for the glass slide. A control of preload was added
consisting of: a spring gauge to the preload force between the
surfaces. The spring gauge consisted of a spring that is translated
to distance when a force is applied. The spring constant was
measured and 20 mN of load translated to 10 units on the dial. As
the spring constant was linear, the amount of preload was varied by
reading the displacement of the dial in the gauge. During testing,
the spring gauge was first brought in light contact with the upper
glass slide. Using the XY stage, the lower glass slide was brought
in contact with the upper glass slide and a displacement shown on
the dial. For all the tests, 30 mN of preload was set (literature
values vary from 20-40 mN). After the preload was set, the spring
gauge was removed to prevent noise from the spring when the tester
was in motion. With the rigid upper clamp, preload was constant
throughout the duration of the tests, maintaining a constant
preload value from sample to sample to compare adhesion values.
Example 3
[0139] The polypropylene pillared substrate prepared as described
in Example 1 as well as its corresponding flat surface film
(unpillared) were tested for shear adhesion against substrates
(sandpaper) with varying surface roughness values under wet
conditions i.e. the substrates and the structures were immersed in
DI water and the mechanical testing was then conducted by the
method described in Example 2. This was done to mimic the wet
conditions that exist in-vivo. The surface roughness value
represents the average feature dimensions expected for different
surfaces. These tests were performed using a mechanical tester sold
under the tradename INSTRON (lnstron Industrial Products, Grove
City, Pa.) and the results are summarized in FIG. 2. The results
clearly show that the flat, unpatterned PP films show uniformly low
adhesion over all substrate roughnesses. The adhesion of the PP
nanopillars (1 micron diameter and 20 microns length) was higher
than its flat counterpart, as well as being a function of the
substrate roughness. Maximum adhesive force was seen on a substrate
roughness of 18 microns.
[0140] From this data we have shown that the dimensions of the
pillar-like protrusions need to be tailored to match the substrate
roughness for maximum adhesion.
Example 4
[0141] The polypropylene pillared substrate prepared as described
in Example 1 as well as its corresponding flat surface film
(unpillared) were tested against, two tissue types, porcine
intestine and porcine bladder for tissue adhesion using the methods
described in Example 5. Adhesive force was measured with a 1.8 kg
(four pound) preload for two minutes. These tissues differ in
characteristics such as elasticity, thickness, and surface
roughness. The shear adhesion data is shown in FIG. 3. The PP film
with 1 micron.times.20 microns pillar-like protrusions can be used
with different tissues. The corresponding polypropylene flat film
provided about 0.14.times.10.sup.4 N/m.sup.2 adhesive force.
Intestine tissue provided about 0.75.times.10.sup.4 N/m.sup.2
adhesive force, while the bladder tissue provided about
0.78.times.10.sup.4 N/m.sup.2 adhesive force.
Example 5
Ex-Vivo Tissue Adhesion Tests
[0142] The aim of this example was to develop an accurate and
reproducible test method to measure shear adhesion to tissue
samples. Shear adhesion values of polypropylene samples of the
present invention against freshly harvested tissue were measured on
a mechanical testing instrument sold under the tradename INSTRON by
Instron Industrial Products, Grove City, Pa. The polymer sample was
made on a polymer substrate and the fresh tissue was soft and
flexible. The tissue was mounted in the apparatus shown in FIG. 4
which comprises a lever arm to press the tissue against the polymer
sample, a pressure transducer to measure pressures generated by the
lever arm and a rigid aluminum backing to provide support for the
soft and flexible tissue to which the tissue was secured to prevent
slippage during the testing process. This also provided a known
contact area of the sample with the tissue. The aluminum holder was
then vertically mounted on the mechanical tester as shown in FIG.
5. The polymer sample was mounted on a glass slide using double
sided tape. The glass slide with the sample was then mounted on the
mechanical tester, and its height was adjusted so that the polymer
sample lined up with the exposed tissue area. The sample was then
gently pressed onto the tissue surface. The lever arm was then
lowered to bring the pressure transducer in contact with the back
of the glass slide. The screw on the lever arm was used to tighten
the glass slide with the substrate mounted against the tissue as
shown in FIG. 5. This was the preload force and could be read on a
digital readout attached to the pressure transducer. This preload
was applied for a specific amount of time with the preload force of
about four pounds and time of about 120 seconds intended to
simulate a person applying a tape or a skin adhesive bandage.
[0143] After the appropriate amount of time, the preload force was
removed by pulling back on the lever arm. The load as read by the
mechanical tester was zeroed and test was then commenced. For the
test method, the glass slide was pulled upwards at the rate of 8
mm/min and the force was recorded. The maximum force was then
recorded as a measure of the shear adhesive force.
Example 6
[0144] The polypropylene samples prepared as described in Example 1
were tested for tissue adhesion against three tissue types i.e.
intestine, bladder and epithelium, using the methods described in
Example 5. The results are shown in FIG. 6. The polypropylene
protrusions or pillars were about one micron in diameter and about
20 microns in length (height) and the intestine and bladder tissues
were smoother than the epithelial tissue which was determined to
have surface roughness of about 5.6 microns to 12 microns as
determined using a surface profiler (NT 9100, Veeco Instruments
Inc, Plainview, N.Y.). The dimensions of the polypropylene
protrusions or pillars appear closer to the surface roughness of
the intestine and bladder tissues, which were determined to have
surface roughnesses of about 0.3 micron to about 1.85 microns and
from about 0.75 micron to about 2.8 microns, respectively.
Consequently, the adhesion values were higher. This behavior was
consistent with the effect seen on adhesion to substrates with
defined rough nesses.
Example 7
[0145] In order to determine the effect of pillar dimensions,
polypropylene samples with different pillar dimensions (about 0.6
micron diameter.times.about 20 microns length and about 5 microns
diameter.times.about 15 microns length) prepared as in Example 1
were tested against two tissue types, i.e., intestine and
epithelium, as described in Example 5. As mentioned earlier, the
intestine tissue was smoother than the epithelial tissue. From the
results shown in FIG. 7, it can be seen that the smaller diameter
pillars show enhanced adhesion to both tissue types. However,
adhesion on the intestine tissue using the 0.6 micron pillars is
2.6 times the adhesion of the bigger five microns pillars. Adhesion
on the epithelial tissue using the 0.6 micron pillars is only 1.5
times the adhesion of the bigger 5 microns pillars. This indicates
that the adhesion enhancement using the smaller diameter, but
taller pillars was greater on the smoother tissue type. Thus the
trend of using nanopillars matching the roughness of the tissue for
enhanced adhesion can be seen in this example.
Example 8
[0146] An experiment was conducted to prepare a polypropylene film
with pillar-like structures on both sides and test its
effectiveness for adhesion to tissue. The polypropylene film with
pillar-like structures on both sides were prepared as follows: A 25
microns thick polypropylene film was compressed under heat and
pressure between two 20 microns thick sheets of polycarbonate
filter material, which polycarbonate filter material thickness
corresponds to the desired length (or height) of the pillar-like
structures to be formed. The filter material possessed microscopic
(0.8 micron) holes, which correspond to the eventual diameter of
the pillar-like structures to be formed. The polypropylene film
melted and flowed into the holes. After processing, the sheet was
annealed. The polycarbonate membrane filter was then dissolved in a
bath of dichloromethane. The membrane filters (0.8 micron ATTP, Cat
No. ATTP14250, Lot No. R9SN70958, available from Millipore
Corporation of Billerica, Mass., USA) possessed two distinct sides,
one having a shiny appearance while the other side was duller. A
laminate for compression molding was constructed as follows: [0147]
a. A segment of polyimide film (sold under the tradename KAPTON by
DuPont, Wilmington, Del.) of 65-70 microns thickness, was placed on
a table; [0148] b. A 15.2 cm (6 inch) polished square metal plate
(thickness 0.8 mm) was placed (shiny side up) on the polyimide
film; [0149] c. A segment of polyimide film was placed on the 15.2
cm (6 inch) plate; [0150] d. A 15.2 cm.times.15.2 cm
(6''.times.6'').times.80 microns steel shim with a 10.1
cm.times.10.1 cm (4''.times.4'') cavity in the center was placed on
the polyimide film; [0151] e. A membrane filter was cut to fit in
the shim cavity and placed (dull side up) on the polyimide film;
[0152] f. A piece of 25 microns thick polypropylene film was cut to
fit in the shim cavity and the sample was placed on the membrane;
[0153] g. Another membrane filter (about 20 microns thick) was cut
to fit in the shim cavity and placed (dull side down) on the
polypropylene film; [0154] h. A segment of polyimide film was
placed on the top membrane; [0155] i. A 15.2 cm (6 inch) polished
square metal plate (thickness 0.8 mm) (shiny side up) was placed on
the polyimide film; and [0156] j. Another segment of polyimide film
was placed on the steel plate.
[0157] Any thermoformable material as previously described can be
substituted for polypropylene as the substrate or core material.
The porous solvent-dissolvable polycarbonate material which acts as
a template for the pillar-like protrusions of the product can be
substituted by another solvent-dissolvable porous polymeric
material. Alternately, a strippable mold such as anodized aluminum
oxide can be substituted to provide the pillar-like cylindrical
protrusions of the final product, without the need for exposure to
a chemical solvent. Polyimide film was used as a capping means or
shield to protect polymer surfaces from directly contacting
surfaces such as metal. Other suitable substantially chemically
inert materials which can also be provided as a film or other layer
for this purpose include polytetrafluoroethylene (sold under the
tradename TEFLON by DuPont, Wilmington, Del.). Advantageously,
these materials are not reactive with the polycarbonate
solvent-dissolvable mold or template material and can be readily
removed or peeled therefrom once compression is completed.
[0158] The resulting sample was loaded into a heated press with
vacuum (less than 150 microns mercury) capability and was processed
as follows: [0159] a. Top and bottom platens were preheated to
190.degree. C. (374.degree. F.); [0160] b. The sample was preheated
under vacuum for 300 seconds prior to any compression; [0161] c.
The sample was compressed at 68948 kPa (10,000 psi) for 300
seconds; [0162] d. Temperature was reduced to 21.degree. C.
(70.degree. F.) while maintaining compression of 68948 kPa (10,000
psi); [0163] e. Compressive force was released and vacuum was
purged; and [0164] f. The sample was removed from the vacuum
press.
[0165] The sample was annealed in the constrained condition
(between two steel plates) in an oven purged with nitrogen gas at
130.degree. C. immediately for two hours. Temperature was reduced
to 100.degree. C. and the sample was annealed at this temperature
for an additional 12.5 hours. Finally, the temperature was slowly
reduced to 25.degree. C. over a period of five hours. The annealing
of the sample was then complete.
[0166] The polycarbonate membrane had been fused to the surface of
the polypropylene film. The membrane was removed by chemical
etching. The membrane was removed from the surface of the
polypropylene film by immersing the sample in a bath of
dichloromethane at room temperature for five minutes. The resulting
sample was allowed to air dry prior to handling. Scanning electron
microscope (SEM) images confirmed the presence of pillar-like
structures which were about 20 microns high and 0.8 microns in
diameter.
[0167] In order to assess the capacity of the modified film to
promote tissue adhesion, a study was conducted. A 2.5 cm by 10.1 cm
(1 inch by 4 inch) section of polypropylene film with pillar
structures was cut from the sheet prepared as described above.
Another 2.5 cm by 10.1 cm (1 inch by 4 inch) sample of 25 microns
thick polypropylene film without pillar structures was used as a
control. Fresh porcine small intestine was cleaned with Phosphate
Buffered Saline (PBS) at room temperature. A section of the
intestine approximately 10.1 cm (4 inches) long was mounted in a
fixture that allowed it to be inflated with air and at the same
time monitored the air pressure within the intestine. A one
centimeter long incision was made in the center of the intestine
segment its length. Fibrin sealant (Human), sold under the
tradename EVICEL by Johnson & Johnson Wound Management, a
division of Ethicon Inc. of Somerville, N.J., USA was prepared in
accordance with the manufacturer's directions. The 5 mL application
device for the sealant was used to aspirate a coating of fibrin
sealant onto the surfaces of both films. The films were then
wrapped around the circumference of the intestine covering the 1 cm
long incision. The films were then clamped in place with a
spring-loaded clamp while the fibrin sealant was allowed to
stabilize for 5 minutes. The sample was then immersed in a PBS bath
maintained at 37.degree. C. and slowly inflated with air
(approximately 5 mm Hg/sec). The air pressure increased until a
maximum value was reached at which point air bubbles were observed
in the PBS bath. The maximum value achieved by the control film
under these conditions was 8.1 mm Hg. The maximum value achieved by
the film with the pillar structures under these conditions was 41.6
mm Hg. The film with the pillar structures was thus able to attain
a burst pressure greater than five times that of the control in
this experiment.
Example 9
[0168] A 100 microns thick polydioxanone film with pillar-like
structures on both sides was prepared. A polydioxanone film was
compressed under heat and pressure between two 20 microns thick
sheets of polycarbonate filter material. The filter material
possesses microscopic (0.8 micron) holes. The polydioxanone film
melted and flowed into the holes. After processing the sheet was
annealed. The polycarbonate membrane filter was then dissolved in a
bath of dichloromethane. The membrane filters used (0.8 micron
ATTP, Cat No. ATTP14250, Lot No. R9SN70958 available from Millipore
Corporation of Billerica, Mass., USA) possessed two distinct sides.
One side had a shiny appearance while the other was duller. A
laminate for compression molding was constructed as follows: [0169]
a. A segment of polyimide film (sold under the tradename KAPTON by
DuPont, Wilmington, Del.) of 65-70 microns thickness was placed on
a table; [0170] b. A 15.2 cm (6 inch) polished square metal plate
(thickness 0.8 mm) (shiny side up) was placed on the polyimide
film; [0171] c. A segment of polyimide film was placed on the 15.2
cm (6 inch) plate; [0172] d. A 15.2 cm.times.15.2 cm
(6''.times.6'').times.80 microns steel shim with a 10.1
cm.times.10.1 cm (4''.times.4'') cavity in the center was placed on
the film; [0173] e. A membrane filter was cut to fit in the shim
cavity and was placed (dull side up) on the polyimide film; [0174]
f. A piece of 25 microns thick polydioxanone film was cut to fit in
the shim cavity. The sample was placed on the membrane; [0175] g.
Another membrane filter (about 20 microns thick) was cut to fit in
the shim cavity and placed (dull side down) on the polydioxanone
film;
[0176] h. A segment of polyimide film was placed on the top
membrane;
[0177] i. A 15.2 cm (6 inch) polished square metal plate (thickness
0.8 mm) (shiny side down) was placed on the polyimide film; and
[0178] j. Another segment of polyimide film was placed on the steel
plate.
[0179] The resulting sample was loaded into a heated press with
vacuum (less than 150 microns mercury) capability and was processed
as follows: [0180] a. The top and bottom platens were preheated to
220.degree. C. (428.degree. F.); [0181] b. The sample was preheated
under vacuum for 300 seconds prior to any compression; [0182] c.
The sample was compressed at 68948 kPa (10,000 psi) for 300
seconds; [0183] d. The temperature was reduced to 21.degree. C.
(70.degree. F.) while maintaining compression of 68948 kPa (10,000
psi); [0184] e. The compressive force was released and the vacuum
was purged; and [0185] f. The sample was removed from the vacuum
press.
[0186] The sample was annealed in the constrained condition
(between two steel plates) in an inert environment (nitrogen gas)
for a minimum of six hours at 70.degree. C.
[0187] The polycarbonate membrane had been fused to the surface of
the polydioxanone film. The membrane was removed by chemical
etching. The membrane was removed from the surface of the
polydioxanone film by immersing the sample in a bath of
dichloromethane at room temperature for five minutes and was
allowed to air dry prior to handling. Scanning electron microscope
(SEM) images of the sample confirmed the presence of pillar-like
structures which were about 20 microns high and 0.8 micron in
diameter.
Example 10
[0188] An anodized aluminum oxide (AAO) mold was prepared for
imprinting of poly(lactic acid) (DL-PLA) polymer into pillar-like
structures. The mold was prepared by forming an AAO film by
electropolishing and etching, and silane-treating the mold by
silane vapor deposition. The resulting mold contains randomly
distributed recesses which provide pillar-like projections in the
demolded product of 200 nanometers by 2 microns. DL-PLA film
obtained from PURAC America of Lincolnshire, Ill., USA and having a
thickness of 100-300 microns is pressed into the AAO mold under
high temperature and pressure in two steps at 100.degree. C. The
first step is carried out at a pressure of 0 kPa (0 bar) for 5
minutes and the second step at 6000 kPa (60 bar) for 20 minutes.
The polymer and mold are cooled to 35.degree. C. before removal of
pressure. Then, the polymer structures are demolded and released by
mechanically peeling them from the mold.
[0189] The resulting demolded DL-PLA polymer structure comprises
pillar-like projections of about 200 nm diameter and about 2
microns length having an aspect ratio (length/diameter) of about
10. FIG. 10 depicts a scanning electron microscope image of the
DL-PLA substrate comprising 200 nm diameter.times.2 microns height
pillar-like protrusions.
Example 11
[0190] The pillared D,L-PLA substrate prepared by the methods of
Example 10 as well as its corresponding flat surface film
(unpillared) were tested for shear adhesion using the methods of
Example 2 against substrates (sandpaper) with varying surface
roughness values. The surface roughness value represents the
average feature dimensions expected for different surfaces. These
tests were performed using a mechanical testing instrument sold
under the tradename INSTRON by Instron Industrial Products, Grove
City, Pa. The results are summarized in FIG. 11 and clearly showed
that the flat, unpatterned PLA films show uniformly low adhesion
over all substrate roughnesses. The adhesion of the PLA nanopillars
(0.2 micron diameter and 2 microns length) was up to 5 times higher
than its flat counterpart, as well as being a function of the
substrate roughness. Maximum adhesive force was seen on a substrate
roughness of 3 microns which is the nearest to the 2 microns height
of the pillar-like protrusions in the structure of Example 10.
[0191] All patents, test procedures, and other documents cited
herein, including priority documents, are fully incorporated by
reference to the extent such disclosure is not inconsistent and for
all jurisdictions in which such incorporation is permitted.
[0192] When numerical lower limits and numerical upper limits are
listed herein, ranges from any lower limit to any upper limit are
contemplated.
[0193] Without further elaboration, it is believed that one skilled
in the art can, using the preceding description, utilize the
present invention to its fullest extent.
[0194] While the present invention has been described and
illustrated by reference to particular embodiments and examples,
those of ordinary skill in the art will appreciate that the
invention lends itself to variations not necessarily illustrated
herein. For this reason, then, reference should be made solely to
the appended claims for purposes of determining the true scope of
the invention.
* * * * *